TB results almost exclusively from inhalation of airborne particles (droplet nuclei) containing M. tuberculosis. They disperse primarily through coughing, singing, and other forced respiratory maneuvers by people who have active pulmonary or laryngeal TB and whose sputum contains a large number of organisms (about 10,000 organisms/mL, the limit of detection by fluorescent microscopy). People with pulmonary cavitary lesions are especially contagious because of the large number of bacteria contained within a lesion.

Untreated active pulmonary TB is highly variable in contagiousness. Certain strains of M. tuberculosis are more contagious, and patients with positive sputum smears are more contagious than those with positive results only on culture. Patients with cavitary disease (which is closely associated with mycobacterial burden in sputum) are more contagious than those without. Respiratory secretions with lower viscosity are more easily aerosolized, and the effectiveness of cough and other respiratory maneuvers in generating aerosol varies greatly.

Environmental factors also are important. Transmission is enhanced by frequent or prolonged exposure to untreated patients who are generating large numbers of tubercle bacilli in overcrowded, poorly ventilated, enclosed spaces; consequently, people living in poverty or in institutions are at particular risk. Health care practitioners who have close contact with active cases have increased risk.